All posts by alp37

Case summary: Thanks to our favorite R3/intern centaur Daniel Kwon, who presented the case of a 60M with PMH HIV on ARVs who presented with dyspnea due to a viral pneumonia and was found to have adrenal insufficiency due to ritonavir potentiation of inhaled nasal steroids!

Top pearls:

In evaluating a patient with hypoglycemia, ensure you confirm Whipple’s triad: 1) hypoglycemia is not a lab error (repeat FSBG and ensure it correlates with serum glucose on a Chem panel), 2) the patient has symptoms of hypoglycemia while hypoglycemic, 3) the patient’s symptoms are relieved with reversal. Finally, if you’re entertaining the diagnosis of insulinoma, ensure you draw the labs for work-up (e.g. C peptide) while the patient is hypoglycemic.

VA hospitalist and medical educator extraordinaire Denise Connor wrote up a fantastic case in JAMA IM reviewing causes of false FSBG readings, which range from shock and PVD to Waldenstrom’s macroglobinemia.

Ritonavir and other CYP450 inhibitors can potentiate the action of steroids that are not typically systemically active (topical, inhaled, nasal) and lead to adrenal insufficiency and iatrogenic Cushing’s syndrome.

Urine studies in hyponatremia due to adrenal insufficiency mimic SIADH (see mechanism below, and thanks to Renal attending Naomi Anker for the teaching!).

Case summary: Thanks to Serge for presenting the case of a 46M with uncontrolled DMT2 presenting with R buttock SSTI, with profound tachycardia, DKA and necrotizing cellulitis.

Top pearls:

1.When evaluating a patient with SSTI who appears ill, be sure to run through the list of SSTI “plus” syndromes that can cause systemic disease and often require additional interventions or consultations: abscess, osteomyelitis, bacteremia, septic joint, tenosynovitis, necrotizing soft tissue infection, pyomyositis, toxic shock syndrome.

2. A shorter mnemonic for AG metabolic acidosis is KULT, which stands for ketones, uremia, lactate and toxins. We like this because it allows you to focus on the most common etiologies and then look up the various toxins included in the lengthy MUDPILERS.

3. The term necrotizing soft tissue infection encompasses not only necrotizing fasciitis (infection of the deep fascia) but also necrotizing myositis (infection of the muscle), and necrotizing cellulitis (infection of the skin that spares the fascia and muscle). Necrotizing cellulitis is typically more indolent and less severe than fasciitis and myositis.

Group B Strep

Most often associated with bacteruria/UTI in pregnant women and neonatal sepsis.

Incidence of infection in non-pregnant adults is increasing (3.6 cases per 100,000 persons during 1990 to 7.3 cases per 100,000 persons during 2007 (P<.001))

See Grant Smith’s great summary post for ALLLLLL you could want to know about necrotizing fasciitis: https://ucsfmed.wordpress.com/2018/01/26/zsfg-am-report-pearls-1-17-2018-almost-doesnt-count-or-does-it-sensitivity-of-ct-for-necrotizing-fasciitis/

Case summary: Thanks to Jake and Taylor for presenting the case of an 88M with new diagnosis of metastatic likely pancreatic adenocarcinoma, who presented with orthostasis 1 day after CT-guided liver mass biopsy, and was found to have bilateral foot and hand edema and obstructive LFTs.

2. Pancreatic cancer has one of the highest risks of VTE of any malignancy (4-7x that of other adenocarcinomas); risk is highest in the 3 months after diagnosis and increases with treatment.

3. Consider paraneoplastic phenomenon when dealing with a patient with cancer + a neurologic, dermatologic or musculoskeletal complaint, as these are the most common systems affected (endocrine and hematologic phenomenon are also possible but less common).

4. RS3PE (remitting seronegative symmetrical synovitis with pitting edema) is a benign, seronegative syndrome of acute onset of pitting edema of the dorsum of both hands and feet and can be idiopathic or paraneoplastic.

5. Malignant biliary obstruction is most often incomplete and intermittent and thus less likely to cause cholangitis than choledocholithiasis.

Paraneoplastic phenomenon

Neurologic

Limbic encephalitis

Cerebellar degeneration

Lambert-Eaton

Myasthenia gravis

Autonomic neuropathy

Sensory polyneuropathy

Dermatologic/MSK

Dermatomyositis

Acanthosis nigricans

Erythroderma

Sweet syndrome

Hypertrophic osteoarthropathy

Paraneoplastic pemphigus

Polymyalgia rheumatica

Rheumatoid arthritis

Reference: Mayo Clinic Proceedings 2010;85(9): 838-854.

Trosseau’s syndrome

Defined as unexplained thrombotic events that precede the diagnosis of an occult visceral tumor or occur concomitantly with the tumor.

Sometimes incorrectly used to refer to any hypercoagulability of malignancy (e.g. from DVT to chronic DIC).

In reality, even this restricted definition encompasses a many disorders with multiple overlapping mechanisms.

Probably best understood as a spectrum of disorders ranging from thrombosis induced by tissue factor produced by the tumor to platelet-rich microthrombi triggered by carcinoma mucins and P- and L-selectins

Case summary: Thanks to our stellar sub-I Ryan Chang with back-up from superb senior Izzy Marshall for presenting a 77M with PMH tobacco use and homelessness who was admitted with scant hemoptysis and L flank pain and found to have metastatic lung adenocarcinoma.

Top pearls:

For non-small cell lung cancer (NSCLC), molecular testing is the key for treatment, with the main prognostic determinants: 1) EGFR mutation (which can be treated with erlotinib), 2) ALK mutation, 3) PDL1 staining

We are moving away from using immunotherapy only in those whose tumors stain positive for PDL1, as some patients who stain negative will still respond to immunotherapy (see 4. below).

All patients with newly diagnosed, later-stage NSCLC should undergo brain MRI given the high incidence of clinically silent brain metastases.

Check out this recent NEJM trial that showed improved overall survival with COMBINATION immunotherapy (regardless of PDL1 staining) and chemotherapy in metastatic lung adenocarcinoma that is EGFR/ALK negative.

NSCLC molecular testing + treatment algorithm

Thanks to Gerald Hsu for these fantastic teaching slides!

See this great NEJM review on NSCLC for more details: Reck M, Rabe KF. N Engl J Med 2017;377:849-861.

Pembrolizumab + chemotherapy has better OS than chemotherapy alone

Double-blind, placebo controlled RCT of ~600 patients with metastatic non-squamous NSCLC (EGFR/ALK negative) who had never been previously treated

Case summary: Thanks to Nick for presenting the fascinating case of a 27F with no PMH who emigrated from India 4 years ago and presented with 1 month of intermittent abdominal pain, 1 week of nausea vomiting, found to have omental nodularity, ascites and partial SBO from abdominal tuberculosis.

Thanks to Jake Mayfield for pointing us in the direction of a systematic review from 2006 that established ADA as having both high sensitivity (99%) and specificity (97%) for diagnosing tuberculous peritonitis

We had two doozies yesterday and today. In this rapid-fire pearls, two become one as we pick out the top learning points from each case!

4.11.18 AM Report

Case summary: Thanks to Karen for presenting the case of a 30F with PMH thyroiditis and celiac disease, who presented with several months of dyspnea and acute hypoxia and was found to have hypersensitivity pneumonitis from marijuana inhalational exposure.

Top pearls:

Keep in mind that in addition to hypoxia causing dyspnea, patients may also have additional features (e.g. elevated lactate) contributing to their sensation of dyspnea.

Recall that CXR can lack sensitivity for significant pathology. The classic cases are interstitial lung disease (as in this patient), immunocompromise and PCP (where up to 30% of patients have a normal CXR).

Inhaled marijuana, synthetic cannabinoids, and their associated smoking devices are emerging triggers for hypersensitivity pneumonitis, either directly or via drug or device contaminants.

4.12.18 Intern Report

Case summary: Alex cared for a 63M with PMH decompensated cirrhosis, ESRD on iHD, and microscopic polyangiitis on steroids, who developed a new leukocytosis and ultimately had ESBL bacteremia and DIC.

Top pearls:

We would not expect chronic steroids to yield a new leukocytosis, as we see this with steroid initiation leading to abrupt (e.g. in <15 min) leukocyte demargination from vessel walls and increased measurement in the serum.

Gerald Hsu gave us some great pointers for distinguishing the coagulopathy of liver disease from DIC:

Always measure a fibrinogen (although this reflects hepatic synthetic dysfunction, baseline levels are usually not low)

See if the patient is bleeding (suggests DIC and also directs therapy)

Tempo of thrombocytopenia (new drop more concerning than stably low)

Measure fibrin degradation products like D-dimer (elevated in DIC but not in cirrhosis)

Yes, Jake Mayfield, like the Jarisch-Herxheimer reaction from penicillin in syphilis, lipopolysaccharide (LPS) released from GNR cell walls after treatment with antibiotics can provoke an inflammatory surge and worsening signs of sepsis. Beta-lactam antibiotics appear to liberate a greater amount of endotoxin compared to other antibiotics.

The major branch points in treating DIC are: 1) Is the patient bleeding? (transfuse), 2) Does the patient have thrombosis? (therapeutic anticoagulation), 3) Neither (prophylactic anticoagulation). See this algorithm based on this breakdown.

Case summary: AJ, Colette and Anne presented a doozy of a case this morning– a 64F with DMT2, HTN and hemorrhoids, who presented with acute R calf pain, R forearm hematoma and hemorrhoidal bleeding and was found to have an isolated prolonged aPTT due to an acquired factor VIII inhibitor (acquired hemophilia A).

Top pearls:

A thorough bleeding history includes questions to distinguish between platelet-associated (e.g. petechiae, mucosal bleeding) and coagluation-associated (e.g. post-traumatic or post-procedural bleeding) symptoms, as well as personal (e.g. prolonged bleeding after surgeries, pregnancy) and family history of bleeding diatheses.

Patients with acquired factor inhibitors (of which inhibitors to 8 are most common) can present with dramatic life- and limb-threatening bleeding and have high morbidity and mortality.

Treatment of acquired factor VIII inhibitor includes immunosuppression with steroids and activated prothrombin complex concentrate (FEIBA) in the presence of major bleeding, which bypasses factor VIII in the coagulation cascade.

Mixing study 101

The first step in work-up of an isolated prolonged aPTT is a mixing study, which Colette explained brilliantly to us.

Step 1: “Mixing study,” which is an inhibitor screen.

If adding normal plasma to a patient’s plasma corrects the aPTT, this suggests a factor deficiency (classically, this would be clear based on history [e.g. consistently prolonged aPTT and history of bleeding diatheses])

If adding normal plasma to a patient’s plasma does not correct the aPTT, this suggests factor inhibitor (factor VIII inhibitors can initially correct and then prolong again, so they require more prolonged incubation)

Step 3: At the VA, the test also includes a DRVVT to test for lupus anticoagulant

Step 4: Finally, the Bethesda Factor VIII Inhibitor Titering Assay tells you the titer of the inhibitor (a confirmatory test for a factor inhibitor that does not correlate with severity and isn’t used to guide intervention)

The skinny on acquired factor VIII inhibitors

This is is an autoantibody against factor VIII in the coagulation cascade.

Can have inherited and acquired inhibitors; of acquired, factor VIII is the most common.

1.3-1.5 cases/million/year and bimodal age distribution (peri-partum in younger women and then in patients >65yo)

Predisposing conditions: ~50% are idiopathic, while the remainder are associated with chronic inflammation–> antibody generation